{"title":"TNF-α-Induced Downregulation of ID2 in Human First Trimester Trophoblast Cells.","authors":"Jiayi Zhou, Yuye Wang, Meitong Chen, Yukako Kayashima, Davin Towenly-Tilson, Monawar Mohamed-Yahia Sadig, Nobuyo Maeda-Smithie, Feng Li","doi":"10.3923/ajbs.2025.323.332","DOIUrl":"10.3923/ajbs.2025.323.332","url":null,"abstract":"<p><strong>Background and objective: </strong>Low levels of Tumor Necrosis Factor-Alpha (TNF-α) support normal pregnancy, while elevated levels are linked to complications like preeclampsia by impairing trophoblast migration and invasion. The study investigates the effect of TNF-α on ID2, a protein associated with trophoblast proliferation, differentiation and stemness, using the HTR8/SVneo cell model.</p><p><strong>Materials and methods: </strong>The HTR8 cells were treated with three different doses of TNF-α (1, 10 and 100 ng/mL) for 4 or 24 hrs. The mRNA and protein levels of ID2 were determined by qRT-PCR and western blot, respectively. Cell viability after exposure to three doses of TNF-α was assessed using the CCK-8 kit. Data are presented as Mean±SEM, analyzed using multifactorial ANOVA with <i>post hoc</i> Tukey-Kramer test in JMP 16.0 (SAS Institute, Cary, NC), considering p<0.05 as statistically significant.</p><p><strong>Results: </strong>Following exposure to three doses of TNF-α for 4 or 24 hrs, both transcriptional and protein levels of ID2 in HTR8 cells were decreased in a dose-independent manner,10 ng/mL of TNF-α had the greatest effects. Additionally, all three doses of TNF-α increased p63 expression as well. Inhibitors of NF-κB or MAPKs did not alter TNF-α-induced decrease in ID2 expression. All three doses of TNF-α increased cell viability to the same level and an inhibitor of IKK/NF-κB, BMS345541, abolished the survival-enhancing effects of the cytokine.</p><p><strong>Conclusion: </strong>The decrease in ID2 expression by TNF-α could be mediated by p63, while the increase in cell survival could be linked to NF-κB activation.</p>","PeriodicalId":521314,"journal":{"name":"Asian journal of biological sciences","volume":"18 2","pages":"323-332"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12993719/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147483226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}